Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Postmortem findings in bustards in the United Arab Emirates

A review was conducted of 236 postmortem examinations of six species of captive and imported bustards in the United Arab Emirates for the period 1979-94. The most common causes of death in adult imported houbara bustards (Chlamydotis undulata macqueenii) were euthanasia due to Newcastle disease, aspergillosis, and post-transportation-related deaths. Helminth parasites were a common finding in imported houbara bustards, and large parasite burdens occasionally caused intestinal obstruction and death. The most common causes of death in adult captive houbara bustards were trauma- related deaths and euthanasia for or death following treatment for capture myopathy. Fatty liver change was an important postmortem finding of captive adult houbara bustards. The main cause of death in juvenile houbara bustards was yolk-sac infection and septicemia. The most common causes of death in adult kori bustards (Ardeotis kori) were capture myopathy and handling injuries or euthanasia following these injuries. The most common causes of death in adult rufous-crested bustards (Eupodotis ruficrista) were post- transportation deaths in imported birds and trichomoniasis and trauma in captive birds. Juvenile rufous crested bustards appeared to be highly susceptible to gizzard impactions and foreign-body obstructions of the gastrointestinal tract. Nutritional hone disease is an important disease of all juvenile bustards, particularly kori and houbara bustards. Aspergillosis was also a common postmortem finding in captive and imported adult houbara bustards and also caused mortality in juvenile kori and houbara bustards

A personalised recommender system for tourists on city trips: concepts and implementation

In this paper we introduce a new recommender system for urban tourists. The goal of the system is to enrich tourists’ experience by offering them personalised tour recommendations tailored to their dynamic user profiles. Particular attention in the proposed approach is paid to the influence of basic leisure needs of an individual, which include new experiences, entertainment, being in open area, relaxation, physical exercise, and socialising, on the tour composition. These needs tend to be dynamic and give rise to saturation effects and variety seeking behaviour. The system is developed as part of the larger c-Space framework, in which a number of technologies, such as projective augmented reality, a newly proposed near real-time 4D dynamic scene reconstruction, and affective computing, are brought together and used to enrich experiences of users in their interactions with built environments. The paper describes the main concepts of the recommender system and its implementation in the specified context of the city of Trento, Italy